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Human Genetics

, Volume 121, Issue 3–4, pp 459–468 | Cite as

The advantages of dense marker sets for linkage analysis with very large families

  • Russell ThomsonEmail author
  • Stephen Quinn
  • James McKay
  • Jeremy Silver
  • Melanie Bahlo
  • Liesel FitzGerald
  • Simon Foote
  • Jo Dickinson
  • Jim Stankovich
Original Investigation

Abstract

Dense sets of hundreds of thousands of markers have been developed for genome-wide association studies. These marker sets are also beneficial for linkage analysis of large, deep pedigrees containing distantly related cases. It is impossible to analyse jointly all genotypes in large pedigrees using the Lander–Green Algorithm, however, as marker density increases it becomes less crucial to analyse all individuals’ genotypes simultaneously. In this report, an approximate multipoint non-parametric technique is described, where large pedigrees are split into many small pedigrees, each containing just two cases. This technique is demonstrated, using phased data from the International Hapmap Project to simulate sets of 10,000, 50,000 and 250,000 markers, showing that it becomes increasingly accurate as more markers are genotyped. This method allows routine linkage analysis of large families with dense marker sets and represents a more easily applied alternative to Monte Carlo Markov Chain methods.

Keywords

Markov Chain Monte Carlo Variance Component Analysis International HapMap Project Large Pedigree Markov Chain Monte Carlo Technique 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The authors would like to thank Terry Speed for his suggestions during the genesis of this project. RT, SQ, JD and JS are supported by an NHMRC Capacity-Building grant, and JS is also supported by an NHMRC Transitional Institute Grant. JM is an NHMRC CJ Martin Fellow.

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Russell Thomson
    • 1
    Email author
  • Stephen Quinn
    • 1
  • James McKay
    • 1
    • 3
  • Jeremy Silver
    • 2
  • Melanie Bahlo
    • 2
  • Liesel FitzGerald
    • 1
  • Simon Foote
    • 1
  • Jo Dickinson
    • 1
  • Jim Stankovich
    • 1
    • 2
  1. 1.Menzies Research InstituteUniversity of TasmaniaHobartAustralia
  2. 2.The Walter and Eliza Hall Institute of Medical ResearchMelbourneAustralia
  3. 3.International Agency for Research on CancerLyonFrance

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